The Neuropathology Core (NPC) supports the clinical and research missions of the UCD ADC by providing (1) expert neuropathological (NP) analysis; and (2) well-preserved brain tissue, along with blood and DNA samples from the clinically well-characterized participants of our longitudinal cohort. In addition, the NPC plays an important role in bolstering basic and translational research on AD and related disorders by providing tissue samples, NP techniques, and NP tools. The UCD NPC has established expertise in postmortem NP analysis, with a special focus on assessment of vascular brain injury. The NPC works closely with the Clinical Core and the Neuroimaging Core to provide clinico-imaging-pathological correlation. The NPC works closely with the Data Management and Statistics Core to incorporate the NP data and tissue information to the web-based UCD ADC database, facilitating research. In collaboration with the Education and Information Transfer Core, the NPC promotes consenting to autopsy by our study subjects, and the use of the NPC resource for research. In the current funding period, we have accomplished all the proposed Aims. We have streamlined our brain and tissue procurement and processing procedures, and obtained more research-grade brain samples. We have collected and banked serum, plasma, and peripheral blood DNA from over 750 individuals participating in UCD ADC-sponsored research protocols. We have made substantial progress in obtaining minority autopsies. We have also developed new research tools such as tissue microarray and multiplex quantification method. Due to our enhanced infrastructure for research, the UCD NPC has become an essential player in the overarching UCD ADC research goal and have contributed to several multi-center projects involving sharing of neuropathological data and samples. Furthermore, there has been a substantial increase in the use of our biological samples by investigators within UCD and outside the ADC. and as a result we supported numerous grants and papers. In this reapplication. we propose to continue all the current aims, with new perspectives and opportunities building on the progress achieved during the current grant cycle.